Naldemedine, a peripherally acting µ-opioid receptor antagonist, was found to be safe and effective for increasing bowel movement frequency and improving quality of life in patients with chronic non-cancer pain and opioid-induced constipation (OIC), in a randomized placebo-controlled phase 3 trial published in Pain. In addition, naldemedine was not found to affect opioid analgesia or to precipitate withdrawal from opioids.
Patients were randomly assigned to receive once-daily 0.2 mg naldemedine (n=623) or placebo (n=623) for 52 weeks.
Patients were eligible to enter the program if they were on a routine laxative regimen, which were allowed to continue during the study period.
Naldemedine’s treatment-emergent adverse events (TEAEs) were the study’s primary outcome. Secondary outcomes were: opioid withdrawal, assessed with the Clinical Opiate Withdrawal Scale and the Subjective Opiate Withdrawal Scale; pain intensity, evaluated with the Numeric Rating Scale; bowel movement frequency; constipation-related quality of life, assessed with the Patient Assessment of Constipation Symptoms scale; and constipation-related quality of life, evaluated with the Patient Assessment of Constipation Quality of Life scale.
At the 52-week follow-up, the incidence of TEAEs was comparable in the 2 groups (naldemedine, 68.4%; placebo, 72.1%) and so was that of TEAEs resulting in therapy discontinuation (naldemedine, 6.3%; placebo, 5.8%).
A greater percentage of patients who received naldemedine vs placebo experienced abdominal pain (8.2% vs 3.1%, respectively), vomiting (6.0% vs 3.1%, respectively), and diarrhea (11.0% vs 5.3%, respectively). Opioid withdrawal and pain intensity levels were comparable in the naldemedine and placebo groups.
The naldemedine treatment resulted in greater improvements in bowel movement frequency, quality of life, and constipation-related symptoms vs placebo (P ≤.0001 for all at all time points).
The investigators obtained data on opioid dose as the dose was prescribed rather than during the actual daily intake. This could have limited the ability of the researchers to determine precise intake in participants.
“This study supports the addition of naldemedine to a patient’s laxative regimen, should patients still experience OIC after self-treating with over-the-counter laxatives,” concluded the study authors.
Webster LR, Nalamachu S, Morlion B, et al. Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic non-cancer pain: a randomized, double-blind, placebo-controlled phase 3 study [published online February 6, 2018]. Pain. doi:10.1097/j.pain.0000000000001174